Clinical Applications of Bio- and Nanomaterials

Established in 2014, the Crielaard group operates on the boundaries of material sciences, pharmaceutical technology and medicine, studying biomaterials and nanosized materials for diagnostic and therapeutic applications. For this aim, we design, develop, and evaluate new 'smart' biocompatible materials and nanoparticles that can be used for drug targeting, drug delivery and medical imaging applications.

The group is embedded in the Department of Polymer Chemistry & Bioengineering at the Zernike Institute for Advanced Materials (ZIAM), University of Groningen, and closely collaborates with the W.J. Kolff Institute of Biomedical Engineering and Materials Science at the University Medical Center Groningen.

The unique interdisciplinary position of our group, connecting the world-leading materials institute ZIAM with its state-of-the-art facilities and the renowned Kolff Institute with its strong clinical focus, provides an excellent scientific infrastructure to allow us to perform high-impact and clinically relevant research.

To further improve clinical translation, we are collaborating with several other research groups that operate in a broad range of scientific fields, including materials science, medicine, pharmaceutics and medical imaging.

Some of our current research interests include:

Targeted therapies

All currently used therapeutic agents have a dose range in which they show beneficial efficacy but not yet have intolerable side effects - the therapeutic window. Typical examples include cancer therapeutics that destroy cancer cells, but also affect healthy cells. This can lead to serious side effects, which often prevent the use of higher, more effective dosing regimes.Drug targeting is used to direct therapeutics to the place in the body where they are needed, such as the cancer tissue, while limiting their localization in healthy tissues. In this way, drug targeting reduces the off-target toxicity and improves the on-target efficacy of drugs, resulting in a better clinical effect and tolerability.

Our group is working on new strategies to target therapeutics by exploiting the differences between healthy and diseased tissues and cells, such as changes in blood vessel leakiness and interstitial pH, the presence of specialized cell types that promote disease activity, or the expression of characteristic molecules on the surface of sick cells

· Macrophage targeting

Literally named 'large eaters' in Greek, macrophages have long been considered relatively simple phagocytic (i.e. eating) cells, cleaning up invading bacteria and other foreign objects that entered our body. However, over the last decades our understanding of the role of macrophages improved, and we realized that macrophages function as key players in many important processes in the body, such as inflammation, cell growth and tissue repair. Moreover, macrophages have also been shown to be involved in the development and progression of a large variety of diseases, such as asthma, rheumatoid arthritis, multiple sclerosis, diabetes mellitus, atherosclerosis, and cancer.

Our group is investigating targeted nanoparticles for modulating the activity of macrophages and limiting their disease-supporting role in cancer, which may be a useful strategy for other disorders as well.

· Targeting the microenvironment

Tumors are relatively fast growing tissues with substantial metabolic activity, while the vasculature if often imperfect with a limited supply of oxygen. This hypoxic state, among other factors, leads to a lowering of extracellular pH, which can be used to trigger tumor-specific (macro)molecular changes in therapeutics and targeting systems, allowing them to stay at the target site, release a therapeutic payload or enter afflicted cells.

In our group we use phage display to identify new small peptides that can be used to target hypoxic, acidic tissues to improve the accumulation of drugs and drug carriers in cancer tissues.

· Targeting cancer cells

A number of forms of cancers (over)express specific antigens, such as a type of receptor, which is not (or little) expressed by healthy cells. This characteristic is currently being used in the clinic to specifically target cancer cells via antibodies, which also known as immunotherapy. In some cases, only targeting and binding of the cancer antigen has therapeutic activity because it blocks cellular signaling pathways essential for its growth or survival, however, it is also possible to attach highly toxic drugs to the targeting ligand to specifically attack cancer cells.

Our group is working on new targeting approaches using peptides and oligonucleotide aptamers to develop synthetic targeted therapeutic agents with tunable physicochemical properties for the treatment of cancer.